HZI Collection: The division is part of HIPShttp://hdl.handle.net/10033/121100
The division is part of HIPSTue, 03 Mar 2015 22:38:39 GMT2015-03-03T22:38:39ZIn vitro surfactant and perfluorocarbon aerosol deposition in a neonatal physical model of the upper conducting airways.http://hdl.handle.net/10033/338661
Title: In vitro surfactant and perfluorocarbon aerosol deposition in a neonatal physical model of the upper conducting airways.
Authors: Goikoetxea, Estibalitz; Murgia, Xabier; Serna-Grande, Pablo; Valls-i-Soler, Adolf; Rey-Santano, Carmen; Rivas, Alejandro; Antón, Raúl; Basterretxea, Francisco J; Miñambres, Lorena; Méndez, Estíbaliz; Lopez-Arraiza, Alberto; Larrabe-Barrena, Juan Luis; Gomez-Solaetxe, Miguel Angel
Abstract: Aerosol delivery holds potential to release surfactant or perfluorocarbon (PFC) to the lungs of neonates with respiratory distress syndrome with minimal airway manipulation. Nevertheless, lung deposition in neonates tends to be very low due to extremely low lung volumes, narrow airways and high respiratory rates. In the present study, the feasibility of enhancing lung deposition by intracorporeal delivery of aerosols was investigated using a physical model of neonatal conducting airways.Wed, 01 Jan 2014 00:00:00 GMThttp://hdl.handle.net/10033/3386612014-01-01T00:00:00ZDevelopment of artemether-loaded nanostructured lipid carrier (NLC) formulation for topical application.http://hdl.handle.net/10033/337849
Title: Development of artemether-loaded nanostructured lipid carrier (NLC) formulation for topical application.
Authors: Nnamani, Petra O; Hansen, Steffi; Windbergs, Maike; Lehr, Claus-Michael
Abstract: NLC topical formulation as an alternative to oral and parenteral (IM) delivery of artemether (ART), a poorly water-soluble drug was designed. A Phospholipon 85G-modified Gelucire 43/01 based NLC formulation containing 75% Transcutol was chosen from DSC studies and loaded with gradient concentration of ART (100-750mg). ART-loaded NLCs were stable (-22 to -40mV), polydispersed (0.4-0.7) with d90 size distribution range of 247-530nm without microparticles up to one month of storage. The encapsulation efficiency (EE%) for ART in the NLC was concentration independent as 250mg of ART loading achieved ∼61%. DSC confirmed molecular dispersion of ART due to low matrix crystallinity (0.028J/g). Ex vivo study showed detectable ART amounts after 20h which gradually increased over 48h achieving ∼26% cumulative amount permeated irrespective of the applied dose. This proves that ART permeates excised human epidermis, where the current formulation served as a reservoir to gradually control drug release over an extended period of time. Full thickness skin study therefore may confirm if this is a positive signal to hope for a topical delivery system of ART.Tue, 30 Dec 2014 00:00:00 GMThttp://hdl.handle.net/10033/3378492014-12-30T00:00:00ZAntibiotic-free nanotherapeutics: Ultra-small, mucus-penetrating solid lipid nanoparticles enhance the pulmonary delivery and anti-virulence efficacy of novel quorum sensing inhibitors.http://hdl.handle.net/10033/332860
Title: Antibiotic-free nanotherapeutics: Ultra-small, mucus-penetrating solid lipid nanoparticles enhance the pulmonary delivery and anti-virulence efficacy of novel quorum sensing inhibitors.
Authors: Nafee, Noha; Husari, Ayman; Maurer, Christine K; Lu, Cenbin; de Rossi, Chiara; Steinbach, Anke; Hartmann, Rolf W; Lehr, Claus-Michael; Schneider, Marc
Abstract: Cystic fibrosis (CF) is a genetic disease mainly manifested in the respiratory tract. Pseudomonas aeruginosa (P. aeruginosa) is the most common pathogen identified in cultures of the CF airways, however, its eradication with antibiotics remains challenging as it grows in biofilms that counterwork human immune response and dramatically decrease susceptibility to antibiotics. P. aeruginosa regulates pathogenicity via a cell-to-cell communication system known as quorum sensing (QS) involving the virulence factor (pyocyanin), thus representing an attractive target for coping with bacterial pathogenicity. The first in vivo potent QS inhibitor (QSI) was recently developed. Nevertheless, its lipophilic nature might hamper its penetration of non-cellular barriers such as mucus and bacterial biofilms, which limits its biomedical application. Successful anti-infective inhalation therapy necessitates proper design of a biodegradable nanocarrier allowing: 1) high loading and prolonged release, 2) mucus penetration, 3) effective pulmonary delivery, and 4) maintenance of the anti-virulence activity of the QSI. In this context, various pharmaceutical lipids were used to prepare ultra-small solid lipid nanoparticles (us-SLNs) by hot melt homogenization. Plain and QSI-loaded SLNs were characterized in terms of colloidal properties, drug loading, in vitro release and acute toxicity on Calu-3 cells. Mucus penetration was studied using a newly-developed confocal microscopy technique based on 3D-time-lapse imaging. For pulmonary application, nebulization efficiency of SLNs and lung deposition using next generation impactor (NGI) were performed. The anti-virulence efficacy was investigated by pyocyanin formation in P. aeruginosa cultures. Ultra-small SLNs (<100nm diameter) provided high encapsulation efficiency (68-95%) according to SLN composition, high burst in phosphate buffer saline compared to prolonged release of the payload over >8h in simulated lung fluid with minor burst. All types and concentrations of plain and QSI-loaded SLNs maintained the viability of Calu-3 cells. 3D time-lapse confocal imaging proved the ability of SLNs to penetrate into artificial sputum model. SLNs were efficiently nebulized; NGI experiments revealed their deposition in the bronchial region. Overall, nanoencapsulated QSI showed up to sevenfold superior anti-virulence activity to the free compound. Most interestingly, the plain SLNs exhibited anti-virulence properties themselves, which was shown to be related to anti-virulence effects of the emulsifiers used. These startling findings represent a new perspective of ultimate significance in the area of nano-based delivery of novel anti-infectives.Tue, 28 Oct 2014 00:00:00 GMThttp://hdl.handle.net/10033/3328602014-10-28T00:00:00ZIn vitro toxicological screening of nanoparticles on primary human endothelial cells and the role of flow in modulating cell response.http://hdl.handle.net/10033/323907
Title: In vitro toxicological screening of nanoparticles on primary human endothelial cells and the role of flow in modulating cell response.
Authors: Ucciferri, Nadia; Collnot, Eva-Marie; Gaiser, Birgit K; Tirella, Annalisa; Stone, Vicki; Domenici, Claudio; Lehr, Claus-Michael; Ahluwalia, Arti
Abstract: After passage through biological barriers, nanomaterials inevitably end up in contact with the vascular endothelium and can induce cardiovascular damage. In this study the toxicity and sub-lethal effects of six types of nanoparticle, including four of industrial and biomedical importance, on human endothelial cells were investigated using different in vitro assays. The results show that all the particles investigated induce some level of damage to the cells and that silver particles were most toxic, followed by titanium dioxide. Furthermore, endothelial cells were shown to be more susceptible when exposed to silver nanoparticles under flow conditions in a bioreactor. The study underlines that although simple in vitro tests are useful to screen compounds and to identify the type of effect induced on cells, they may not be sufficient to define safe exposure limits. Therefore, once initial toxicity screening has been conducted on nanomaterials, it is necessary to develop more physiologically relevant in vitro models to better understand how nanomaterials can impact on human health.Mon, 01 Sep 2014 00:00:00 GMThttp://hdl.handle.net/10033/3239072014-09-01T00:00:00Z